Straight to the Heart
New Study Uses Stem Cells to Repair Heart Muscle

Six months ago, Nelson Aguia was preparing to die. Suffering from end-stage heart failure, the 68-year-old resident of Rio de Janeiro, Brazil was too weak to walk from one room to the next or finish a sentence without excruciating chest pain and shortness of breath.

Doctors had tried all the conventional therapies to help him recover from two previous heart attacks, including bypass surgery, angioplasty, and medication, but nothing worked.

"I was told to prepare for one final, fatal heart attack," said Aguia. "There was nothing left to do but lie in bed and wait to die."

Then, last fall, Aguia’s daughter who is a pediatrician in Brazil, read a newspaper article about an experimental trial that she believed could provide her father with one last chance for recovery.

"I never accepted the fact that my father would die ... I always held out hope," said Terezinha Aguia, who her father affectionately calls his "guardian angel."

At Terezinha’s urging, doctors at Pro-Cardiaco Hospital in Rio de Janeiro offered the fast-failing Aguia an opportunity to become the first of 15 patients enrolled in what is believed to be the largest cardiovascular stem cell study in the world.

In a collaborative effort between Houston’s Texas Heart Institute and Pro-Cardiaco Hospital, Houston doctors have been making frequent trips to Brazil during the six months since the study began to treat damaged human hearts with stem cells taken from the patients’ own bone marrow. The goal of the study is to assess whether stem cells taken from bone marrow, then implanted in the heart, can help strengthen damaged heart muscle.

Aguia received the therapy in December. Six months later, he is walking three miles around Brazil’s largest soccer stadium twice a week, swimming three times a week, and working eight hours a day as a pharmaceutical sales representative – a job he gave up years ago.

When the Brazilian soccer team competes for the world cup this month, he’ll be cheering with other die-hard fans at pre- and post-game parties. When Rio de Janeiro’s famous Carnival gets under way next February, he’ll dance three hours in the streets – the length of time it takes to complete the parade route.

"I’m ready for anything. This treatment has restored my life," said a grateful Aguia.

Dr. James Willerson, medical director and director of cardiology research at Texas Heart Institute, says it’s still very early to make firm conclusions.

"I can tell you, though, that we are seeing improvements in these patients. We are very encouraged," he said.

Data generated from the study will be presented at this November’s meeting of the American Heart Association, said Dr. Willerson, who is also president of The University of Texas Health Science Center in Houston.

To date, 10 patients – four in December and another six this April – have received the stem cell therapy, and are being compared to another five who are not receiving the treatment. Most who were treated with stem cells experienced improvement over a period of 12 weeks. All are still alive, although they were near death when treatment began.

The fact that no deaths have occurred is worth noting, said Dr. Emerson Perin, director of New Interventional Cardiovascular Technology at the Texas Heart Institute. Dr. Perin, a native Brazilian who maintains close clinical and research ties with Pro-Cardiaco Hospital, is performing the clinical procedures in Brazil.

"This is encouraging news for these patients. Until now, they had absolutely no remaining treatment options. They had reached the end of the road in terms of what we could offer to them."

All patients enrolled in the study have "triple-vessel" disease, meaning their major coronary arteries are occluded and blood flow is prevented or severely hindered. All have had heart attacks and undergone bypass surgery, only to have their arteries re-occlude.

"They were living off borrowed time," said Dr. Perin.

Although early findings from the stem cell study are generating a rousing response from the scientific community and daring patients to hope, Dr. Perin cautions against becoming too enthusiastic too early.

"If this therapy works in our small group of study participants, the next step is to conduct the same study in a much larger number of patients, probably 200 or so," he explained. "We’ll need to do a multicenter trial involving several centers in the United States and around the world."

The treatment is minimally invasive, and uses a catheter to carry harvested bone marrow stem cells straight to the heart. Under the right conditions, stem cells will potentially give rise to, or differentiate into, the cell types that make up the organism into which they are injected – in this case, the heart muscle.

"The goal of this treatment is to replace damaged heart muscle cells and promote the growth of new blood vessels that will supply oxygen to the damaged heart muscle. The stem cells are going ‘to the rescue’ to accomplish this," explained Dr. Perin.

To conduct the procedure, doctors harvest stem cells from a patient’s bone marrow, select out those cells most likely to develop into the cell type needed in the heart, culture them for three hours, then inject the cells into the heart.

The cells are carried to the left ventricle – the main pumping chamber of the heart – by way of a narrow catheter that is inserted into a tiny incision in the patient’s groin and threaded upward through the body, into the heart. A needle then is sent traveling through the catheter until it emerges into the left ventricle, at the catheter’s end.

Using a 3-D map of the heart illuminated on a video screen, doctors identify the areas of the heart that are suffering the most and target those specific areas for injection.

"We make sure the catheter’s tip is perfectly situated against the heart wall, then we inject the needle into the heart muscle, delivering millions of stem cells to that one little spot," explained Dr. Perin.

Injections are placed into the areas of the heart that are in greatest need of repair. In Aguia’s case, 11 sites within his heart were targeted.

To prevent infection, the entire procedure – from harvesting bone marrow to injecting stem cells – is done in one day.

"Take the cells out of the marrow, get them into the heart quickly – that’s the goal. The longer the cells are exposed, the greater the risk of infection," explained Dr. Perin.

Similar stem cell treatment trials are under way in Hong Kong, Australia and the Washington Hospital Center in Washington, D.C., but with different types of stem cells.

The Brazilian therapy began with Texas Heart Institute animal research conducted by Dr. Willerson and Dr. Yong J. Geng, director of the institute’s heart failure laboratory, in which stem cells from dog embryos were used to treat adult dogs with heart attacks. After two weeks of treatment, scar tissue which forms where heart muscle dies after a heart attack was reduced in the adult dogs by 30 percent.

Drs. Willerson and Perin praise the therapy because it is inexpensive, simple to perform, and poses no risk of rejection, since patients are donating their own cells.

The study, Dr. Perin said, is being done "on a shoestring," without formal funding.

"I donate my time and travel, the doctors in Brazil donate their lab space and cell culture expertise, the Pro-Cardiaco Hospital provides the patients and operating rooms, and Johnson & Johnson donates the medical equipment to carry out the treatments. Basically, we’re all doing this without cost. That’s a story in itself."

When the data is published later this year, Drs. Willerson and Perin hope the findings will lead to funding for larger, more extensive trials from organizations such as the National Institutes of Health and the American Heart Association. They also believe this study should prompt the Food and Drug Administration to quickly approve a trial in the United States.

Dr. Willerson said another 10 Brazilian patients probably will be added to the study and receive injections in August. He hopes the investigational treatment will become available to patients at the Texas Heart Institute by the end of this year.

Eventually, he believes the therapy can be expanded to deliver new genes – gene therapy – to the heart.

"Someday we’ll be placing genes

in the heart to carry out important functions, such as preventing blood clots, protecting against scarring, and preventing arteries from renarrowing," he predicts.

Nelson Aguia describes the therapy’s future as "wonderfully promising" as he plans "the biggest, grandest, most spectacular" celebration to commemorate his upcoming 50th anniversary to his wife Carmen.

"And to think, I was first in line when this all began."

EDITOR’S NOTE – A special thank you to registered nurse Rosa Frimm with St. Luke’s Episcopal Hospital’s international services department, for her assistance with language translation.

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©2006 Texas Medical Center

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